BMP signaling pathway in eyelid development (WP3663)

Mus musculus

The signaling pathways involved in eyelid development are displayed with interactions that are known (solid arrows) and proposed (dotted arrows). The four main pathways shown are activated by Fgf10 and regulate key processes, but also interact with each other. The first pathway is a proposed promotion of sfrp1 which inhibits Wnt that regulates the Meibomian Gland. The Wnt pathway also activates pitx2 and begins the proposed pathway to eyelid closure. The second pathway begins with Fgfr2 activating Bmp4, a protein that may also be regulated by Shh, and continuing through a protein chain to regulate conjunctival cell fate. In this pathway Bmp also inhibits transdifferentiation of Meibomian Gland into a hair follicle, conjunctiva proliferation, and precocious differentiation. The last two pathways are linked to the regulation of eyelid closure through a cascade of protein activation and is further promoted by Bmp through stimulation of phosphorylated c-Jun. This pathway is based on figure 10B from Huang et al.


AAR&Co , Linda Rieswijk , Kristina Hanspers , Denise Slenter , Eric Weitz , and Egon Willighagen


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Mus musculus



Pathway Ontology

signaling pathway pertinent to development


Label Type Compact URI Comment
Fgf10 GeneProduct ensembl:ENSMUSG00000021732
Fgfr2 GeneProduct ensembl:ENSMUSG00000030849
Activin beta-B GeneProduct ensembl:ENSMUSG00000037035
Tgfa GeneProduct ensembl:ENSMUSG00000029999
Shh GeneProduct ensembl:ENSMUSG00000002633
Bmp4 GeneProduct ensembl:ENSMUSG00000021835
Sfrp1 GeneProduct ensembl:ENSMUSG00000031548
Smad1 GeneProduct ensembl:ENSMUSG00000031681
Smad5 GeneProduct ensembl:ENSMUSG00000021540
Smad4 GeneProduct ensembl:ENSMUSG00000024515
Pitx2 GeneProduct ensembl:ENSMUSG00000028023
Dkk2 GeneProduct ensembl:ENSMUSG00000028031
Foxc1 GeneProduct ensembl:ENSMUSG00000050295
Foxc2 GeneProduct ensembl:ENSMUSG00000046714
Notch GeneProduct ensembl:ENSMUSG00000026923 Notch Not Specified
MEKK1 GeneProduct ensembl:ENSMUSG00000021754
JNK GeneProduct ensembl:ENSMUSG00000020366 JNK Not Specified
p-c-Jun GeneProduct ensembl:ENSMUSG00000052684
Egfr GeneProduct ensembl:ENSMUSG00000020122
ERK GeneProduct ensembl:ENSMUSG00000063065 ERK Not Specified


  1. FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate. Huang J, Dattilo LK, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, et al. Development. 2009 May;136(10):1741–50. PubMed Europe PMC Scholia